Activation of CD8<sup>+</sup> T Cells in Chronic Obstructive Pulmonary Disease Lung
Authors: Ana B. Villaseñor-Altamirano, Dhawal Jain, Yunju Jeong, Jaivardhan A. Menon, Mari Kamiya, Hibah Haider, Reshmi Manandhar, Muhammad Dawood Amir Sheikh, Humra Athar, Louis T. Merriam, Min Hyung Ryu, Takanori Sasaki, Peter J. Castaldi, Deepak A. Rao, Lynette M. Sholl, Marina Vivero, Craig P. Hersh, Xiaobo Zhou, Justus Veerkamp, Jeong H. Yun, Edy Y. Kim, Markus Koch, Alessandro Arduini, Hana Cernecka, Nicole Schmidt, Alexis Laux-Biehlmann, Damian Brockschnieder, Xiaofei Cong, Anna Engler, Mahmoud Ibrahim, Dhawal Jain, Ivan Kryukov, Kuldeep Kumawat, T. Lang, Yelena Leathurby, Xin Lin, Joerg Meding, Carlos Neideck, Kseniya Obraztsova, C. Pavuluri, Magdalena Platzk, Patrick Smith, Florian Sohler, Salil Srivastava, P. Srinivasa, Tobias Strunz, Jody Sylvia, Lea Vaas, Justus Veerkamp, Alex Zink, Lingyao Zhang, L. Zeng, Xin Lin, Edwin Silverman, Vincent Carey, Peter Castaldi, Michael Cho, Dawn DeMeo, Craig Hersh, Brian Hobbs, Matthew Moll, Heena Rijhwani, Jeong Yun, Xiaobo Zhou, Bruce D. Levy, Yohannes Tesfaigzi, Humra Athar, Yan Bai, Rebecca Baron, Tracy Doyle, Souheil El-Chemaly, Laura Fredenburgh, G. Matt Hunninghake, Yunju Jeong, Edy Y. Kim, Nandini Krishnamoorthy, Yohannes Mebratu, Mark Perrella, Joselyn Rojas Quintero, Zerihun Negasi, Mizanur Rahman, Dereje Tassew, Nirmal Sharma, Tomoyoshi Tamura, Ana B. Villaseñor-Altamirano, Benjamin Medoff, Elizabeth Abe, Katherine Black, Corey Hardin, Rachel Knipe, Barry Shea, Jill Spiney, Mahaa Albsuharif, Francesca Giacona, Armin Jayaswai, Greg Keras, Sool Lee, Jianyuan Liu, Chandan Pavuluri, Betty Pham, Samuel Saliba, Pooja Srivastava, Yichao Wang, Shuang Xu
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), the immune cell landscape in the lung tissue of patients with mild-moderate disease has not been well characterized at the single-cell and molecular level. Objectives: To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. Methods: We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD (n = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction (n = 5), end-stage COPD (n = 2), control (n = 6), or donors (n = 4). We validated in an independent patient cohort (N = 929) and integrated with the Hhip+/− murine model of COPD. Measurements and Main Results: Mild-moderate COPD lungs have increased abundance of two CD8+ T cell subpopulations: cytotoxic KLRG1+TIGIT+CX3CR1+ TEMRA (T effector memory CD45RA+) cells, and DNAM-1+CCR5+ T resident memory (TRM) cells. These CD8+ T cells interact with myeloid and alveolar type II cells via IFNG and have hyperexpanded T-cell receptor clonotypes. In an independent cohort, the CD8+KLRG1+ TEMRA cells are increased in mild-moderate COPD lung compared with control or end-stage COPD lung. Human CD8+KLRG1+ TEMRA cells are similar to CD8+ T cells driving inflammation in an aging-related murine model of COPD. Conclusions: CD8+ TEMRA cells are increased in mild-moderate COPD lung and may contribute to inflammation that precedes severe disease. Further study of these CD8+ T cells may have therapeutic implications for preventing severe COPD.